ArticleThe Journal of clinical investigation2025
Macrophage-mediated IL-6 signaling drives ryanodine receptor-2 calcium leak in postoperative atrial fibrillation.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Inflammation and day-to-day occurrence of atrial fibrillation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Trial
- Molecular mechanisms, therapeutic strategies, and inter-organ fibrosis crosstalk of Gla proteins in cardiovascular disease.Communications biology · 2026Review
- The Immune System as a Proarrhythmic Mediator: A Novel Paradigm for the Development of New Antiarrhythmic Therapy.The Canadian journal of cardiology · 2026Review
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- 'A leukin to the future': is low serum interleukin-2 (IL-2) a predictive biomarker for postoperative atrial fibrillation?International journal of cardiology. Heart & vasculature · 2026Article
- G protein-coupled receptors and inflammation resolution signaling networks in the heart: Pharmacology and potential for innovative therapeutics.Pharmacological reviews · 2026Review
- Neuroimmune interactions in cardiovascular homeostasis and disease.American journal of physiology. Cell physiology · 2026Review
- Molecular Mechanisms and Therapeutic Strategies in Heart Failure Due to Dystrophin Deficiency: A Comprehensive Review.Reviews in cardiovascular medicine · 2026Review
- Atrial fibrillation and metabolic syndrome: an updated review of mechanisms, risk factors, and therapeutic strategies.Frontiers in cardiovascular medicine · 2026Review
- Inflammatory Biomarkers in the Assessment of Kidney Function Decline in Long COVID Syndrome.Kidney & blood pressure research · 2026Observational
- Arrhythmogenic Mechanisms of Novel Biomarkers in Cardiac Electrophysiology.Cardiology research and practice · 2026Review
- Cardiac resident macrophages: the emerging role in arrhythmogenesis.Frontiers in immunology · 2026Review
- Norepinephrine promotes the proliferation, migration, and phenotypic transformation of renal artery vascular smooth muscle cells via ROCK1.Iranian journal of basic medical sciences · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Macrophage Migration Inhibitory Factor: the Next Adjunct to Reperfusion Therapy in Acute Myocardial Infarction?Cardiovascular drugs and therapy · 2025Article
- Article
- Atrial fibroblast-derived macrophage migration inhibitory factor promotes atrial macrophage accumulation in postoperative atrial fibrillation.JCI insight · 2025Article
- Immune cells and arrhythmias.Cardiovascular research · 2025Review
- Development and Validation of a Risk Prediction Model for New-Onset Atrial Fibrillation in Sepsis.International journal of general medicine · 2025Article
- GJA5 and ATP1A1 perturbations recapitulate inflammation-related beat irregularities in iPSC-based atrial myocardium tissue model.Frontiers in immunology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
Postoperative atrial fibrillation (poAF) is AF occurring days after surgery, with a prevalence of 33% among patients undergoing open-heart surgery. The degree of postoperative inflammation correlates with poAF risk, but less is known about the cellular and molecular mechanisms driving postoperative atrial arrhythmogenesis. We performed single-cell RNA-seq comparing atrial nonmyocytes from mice with and without poAF, which revealed infiltrating CCR2+ macrophages to be the most altered cell type. Pseudotime trajectory analyses identified Il-6 as a gene of interest driving in macrophages, which we confirmed in pericardial fluid collected from human patients after cardiac surgery. Indeed, macrophage depletion and macrophage-specific Il6ra conditional knockout (cKO) prevented poAF in mice. Downstream STAT3 inhibition with TTI-101 and cardiomyocyte-specific Stat3 cKO rescued poAF, indicating a proarrhythmogenic role of STAT3 in poAF development. Confocal imaging in isolated atrial cardiomyocytes (ACMs) uncovered what we believe to be a novel link between STAT3 and CaMKII-mediated ryanodine receptor-2 (RyR2)-Ser(S)2814 phosphorylation. Indeed, nonphosphorylatable RyR2S2814A mice were protected from poAF, and CaMKII inhibition prevented arrhythmogenic Ca2+ mishandling in ACMs from mice with poAF. Altogether, we provide multiomic, biochemical, and functional evidence from mice and humans that IL-6-STAT3-CaMKII signaling driven by infiltrating atrial macrophages is a pivotal driver of poAF, which portends therapeutic utility for poAF prevention.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.